This invention relates to the extracorporeal treatment of blood, and more particularly to the blood access for Renal Replacement Therapy or treatments using an artificial kidney. It is also related to the treatment of congestive heart failure and fluid overload in a patient.
Renal Replacement Therapy (RRT) is a class of medical treatments that artificially provide functions that would naturally be provided by the kidneys. Mechanical RRT generally involves an extracorporeal blood circuit that treats blood that is temporarily removed from and then returned to a patient. RRT performs two primary functions: (i) ultrafiltration (removal of water from blood plasma), and (ii) solute clearance (removal of different molecular weight substances from blood plasma). Devices used for RRT generally include: an extracorporeal blood circuit that extends from the patient through a filter and back to the patient; a pump acting on the blood circuit tube that moves the blood through the tube and filter, and a filter where the blood components are separated and where the solute exchange takes place. In addition, a RRT device may include a controller to regulate the pumps, which in turn control the flow rate of blood and other fluids through the circuit, and detect blockages and leaks in the blood circuit.
In operation, blood from a patient flows through the RRT blood circuit at a flow rate determined by the pump speed. As the blood flows through the filter, certain fluids, solutes or both from the blood pass through the filter membrane and are extracted from the blood plasma. The extracted fluids with solutes flow from the filter through a filtrate tube and are temporarily stored in a filtrate bag. The extraction of fluids and/or solutes by the RRT device replaces or supplements the natural functions of the kidneys. Fluids may be injected into the remaining blood plasma which then flows through the blood circuit tube and is infused into the patient.
The filter in an RRT device, also called hemofilter or xe2x80x9cdialyzerxe2x80x9d, can be set up to perform fluid removal, solute clearance, or both. The RRT device may also operate with or without fluid replacement. xe2x80x9cClearancexe2x80x9d and xe2x80x9cultrafiltrationxe2x80x9d are common terms used in RRT. xe2x80x9cClearancexe2x80x9d is the term used to describe the net removal of substances, both normal and waste product, from the blood. xe2x80x9cUltrafiltrationxe2x80x9d is the term used to describe the removal of plasma water, without significant affect on the concentration of small solutes in blood plasma, from the blood plasma. In mechanical terms xe2x80x9cUltrafiltrationxe2x80x9d is the convective transfer of fluid out of the plasma compartment of a filter through pores in the filter membrane and into a filtrate output compartment of the filter.
Blood filters generally have a blood compartment having input and output ports connected to the blood circuit, a filter membrane, and a filtrate compartment. The membrane separates the blood compartment and the filtrate compartment in the filter. In a filter used primarily for ultrafiltration, the pores of the filter membrane may be hollow fibers having blood passages of approximately 0.2 mm or less in diameter. The filter membrane pass fluids, electrolytes and small and middle sized molecules (typically up to 50,000 Daltons) from the blood plasma. The ultrafiltrate output from the filtration pores is similar to plasma, but without the plasma proteins or blood cells. In an ultrafiltration filter, the concentration of small solutes is the same in the ultrafiltrate as in the plasma, and, thus, no clearance or concentration change is obtained of small solutes in the blood plasma that is returned to the patient. However, the ultrafiltration does remove water from the blood and is useful for treating patients suffering from fluid overload. During the ultrafiltration treatment of a fluid overloaded patient the fluid that is mechanically xe2x80x9cfilteredxe2x80x9d or removed from blood is typically immediately replaced by the access fluid that has been stored in the body. As a result the excess fluid or xe2x80x9cedemaxe2x80x9d in the legs, the abdomen and the lungs of the patient is reduced and the patient""s condition is relieved.
Dialysis is a different form of RRT. Dialysis is the transfer of small solutes out of a blood plasma compartment of a filter by diffusion across the filter membrane. Dialysis occurs as a result of a concentration gradient across the filter membrane. Diffusion of small solutes occurs from the filter compartment with a higher concentration (typically the blood compartment) to a compartment with lower concentration (typically the dialysate compartment). Since the concentration of solutes in the plasma decreases, clearance is obtained. Fluid removal does not necessarily occur during dialysis.
Ultrafiltration can be combined with dialysis to remove both fluid and small solutes from the blood plasma during RRT. Hemofiltration is the combination of ultrafiltration and fluid replacement. The volume of the replacement fluid is typically much larger than is needed just for fluid control. The replacement fluid generally contains electrolytes, but not other small molecules. There is some clearance because there is a net removal of small solutes due to both replacing fluids without small solutes and ultrafiltration of fluid with small solutes. A primary difference between the ultrafiltration and hemofiltration treatments is that during the former the plasma water removed from blood is replaced by the natural excess fluid internally stored in the patient""s body. During the later the replacement solution is supplied by the treatment in a form of an artificial infusion.
Generally, all modes of Renal Replacement Therapy involve the removal of blood (typically venous) from a patient and passing the blood through a hollow fiber filter where there occurs fluid removal and, if desired, a solute removal or exchange. After passing through the filter, the blood is returned to the blood stream of the patient. So-called xe2x80x9cbatchxe2x80x9d type RRT devices extract and return blood through the same single lumen IV catheter or xe2x80x9cneedlexe2x80x9d and blood tube by reversing the direction of the blood pump. More common xe2x80x9ccontinuousxe2x80x9d type devices extract and return blood continuously using one double lumen catheter in the same vein or separate catheters in two separate veins. Catheter and needles used in RRT are generally known as xe2x80x9cblood accessxe2x80x9d. Some RRT patients have permanently lost their kidney function and need to undergo dialysis several times a week. These patients typically have surgically implanted or modified sited for blood access such as arterial-venous shunts or fistulas.
Another large group of xe2x80x9crenalxe2x80x9d patients do not have permanent kidney damage. These renal patients have generally healthy kidneys that are not fully functioning, and the kidneys that have allowed the patient to become overloaded with fluids and toxic solutes. These patients require temporary support by an artificial kidney. Some of these patients suffer from Acute Renal Failure (ARF) in which their natural kidneys no longer have the ability to remove excess fluid and toxic solute from their blood stream for days or even weeks. These patients temperately require a RRT that removes both fluids and solutes from the blood stream.
Another large group of patients, who can benefit from fluid removal by ultrafiltration of blood, have functional kidneys, but suffer from fluid overload due to Congestive Heart Failure (CHF). The kidneys of CHF patients are generally healthy but are not fully functioning due to the failing heart and low blood pressure. Because the kidneys are not fully functioning, fluids build up in the patient and the fluid overload contributes to the stress on the already failing heart. However, the kidneys do make some urine that is usually sufficient for the kidneys to remove toxic solutes.
CHF patients need an RRT treatment that removes excess fluid from the body. These patients typically do not require solute removal or a long-term chronic treatment. The fluid can be removed from the patient relatively quickly and the treatment stopped. The reduction of fluid overload should relieve the stress on the heart sufficiently so that the heart is again able to resume adequate perfusion of the kidney. Even if the heart is unable to adequately perfuse the kidney after the fluid overload treatment, the patient often enjoys several days or weeks before the fluid overload condition again becomes sufficiently severe to undergo another ultrafiltration treatment. These CHF patients need an RRT treatment that is simple to establish and safe.
CHF is a condition that occurs when the heart becomes damaged and reduces the blood flow to other organs of the body, including the kidneys. To operate properly, the kidneys require a certain blood flow and perfusion pressure. If the blood flow decreases sufficiently, the kidneys are not adequately perfused and kidney function becomes impaired. Due to the impaired kidney functions, the patient suffers from fluid retention, abnormal hormone secretions and increased constriction of blood vessels. These results from impaired kidney functioning increase the workload of the heart and further decrease the heart""s pumping ability. Due to the added work from the poor kidney function, the already-failing heart further reduces the blood flow and pressure. It is believed that the progressively-decreasing perfusion of the kidney is a principal non-cardiac cause perpetuating the downward spiral of the xe2x80x9cVicious Cycle of CHFxe2x80x9d. Moreover, the fluid overload and associated clinical symptoms resulting from these physiologic changes are the predominant cause for excessive hospital admissions, terrible quality of life and overwhelming costs to the health care system due to CHF.
Fluid overload can lead to several painful and dangerous conditions, including excessive fluids in the lungs. If excessive fluid in the lungs is not promptly removed with a diuretic medication, CHF patients are often intubated and placed on a ventilator. If the initial diuretic therapy has little affect, more aggressive treatment with increasingly potent diuretics is needed. In addition, inotropic agents such as dobutamine are administered to increase the pumping function of the heart and raise the blood pressure. Higher blood pressure is expected to assist in the perfusion of the kidneys and make diuretics work. In more recent years, vasodilator therapy became a part of the standard therapy for a severely volume-overloaded, decompensated CHF patient. All the above-mentioned therapies as a rule require admission to an intensive care unit (ICU) of a hospital. Potentially dangerous side affects of drugs and the need for advanced monitoring and intubation are the main reasons for a typical ICU admission. However, ICU admissions are expensive and require specialized doctor and nurse caregivers.
The primary causes of admission in CHF patients are symptoms of severe shortness of breath from fluid overload in the lungs. Symptoms of fluid overload are excessive fluid retained in the abdomen, legs and lungs. Of these, fluid in the lungs is the most dangerous and can cause patients to have difficulty breathing. Fluid or xe2x80x9cedemaxe2x80x9d in the lungs leads to poor blood oxygenation. Poor oxygenation leads to acidosis and deleterious neurological and hormonal phenomena that increases vasoconstriction and load on the heart. In addition, vasoconstriction leads to reduced blood flow to the kidneys and diminishes the effectiveness of the main pharmacological means of fluid removalxe2x80x94diuretic treatment. This phenomenon is known as the xe2x80x9cvicious cyclexe2x80x9d of CHF heart failure. Accordingly, there is a need for a simple and effective treatment to quickly relieve fluid overload and particularly to remove excessive fluid from the lungs.
Previously, standard drug therapy was frequently unable to remove excess fluid rapidly enough to prevent hospitalization. There is a clear and unmet clinical need for a CHF treatment that allows physicians to rapidly, controllably and safely remove a clinically significant amount of fluid from a CHF patient. Such a treatment would potentially reduce the need for excessive hospital admissions and decrease the duration of hospital stays.
Ultrafiltration (one mode of Renal Replacement Therapy) is useful for removal of excess fluid from a patient, especially in CHF patients whose kidneys are not working but are generally healthy. Ultrafiltration has not been used widely in the treatment of patients with CHF, despite its clinical benefits for treating fluid overload. There are several issues that have in the past limited the use of currently available ultrafiltration devices. One of these factors is that prior ultrafiltration devices draw large blood volumes of blood out of the body and, thus, require so called central venous access. Central venous access implies that a relatively large diameter catheter is placed with its tip in a major vein in the xe2x80x9ccenterxe2x80x9d of the patient""s body. Typically the central catheter is placed in the superior vena cava or right atrium of the heart of the patient. To place the catheter, a physician makes a percutaneous tunnel under fluoroscopic guidance into an internal jugular vein, external jugular vein or a subclavian vein. The right internal jugular vein is the preferred insertion site. This approach offers a curved route to the superior vena cava. The catheter tip should reside at the junction of the superior vena cava and right atrium or in the right atrium to ensure a high blood-flow rate. This just-described procedure requires high skill. It is also associated with serious complications such as bleeding, perforated lung or heart and infections. As a result, mechanical fluid removal in CHF patients has in the past been used in the ICU of a hospital where resources, training and adequate nursing monitoring are available.
With the increasing prevalence of decompensated CHF and the increased cost of hospital admission and even more so of an ICU treatment, a strong need has emerged for a new technology that will allow fluid removal in the non critical care setting. This need is for a device and technique that is simple and safe so that it could be used in the outpatient setting, doctor""s offices, Emergency Rooms (ER) and general hospital floors. Such treatment would be acceptable if access to venous blood was established via a peripheral vein in the patient""s arm or other peripheral vascular site on the patient. An advantage of accessing blood through a peripheral vein in the arm is well recognized. Unlike the central veins, the peripheral veins are close to skin and easy to identify. Physicians and nurses are trained to place needles and catheters in the peripheral veins of an arm. Venopunctures are easy to monitor for infiltration of fluid and thrombosis and the control of infection is simpler than with central catheters. Also, potential loss of a peripheral vein to thrombosis is less critical.
Recently, applicants invented an ultrafiltration technique that relies on peripheral vein access. This ultrafiltration technique is described in commonly-owned U.S. Pat. No. 6,533,747 and entitled xe2x80x9cExtracorporeal Circuit for Peripheral Vein Fluid Removalxe2x80x9d, the entirety of which is incorporated by reference, and in (now pending U.S. patent application Ser. No. 09/618,759, filed Jul. 18, 2000) and entitled xe2x80x9cMethod and Apparatus for Peripheral Vein Fluid Removal in Heart Failurexe2x80x9d, the entirety of which is incorporated by reference. The volume of blood that can be drawn from a peripheral vein is substantially less than can be drawn from a central access vein. Nevertheless, the relatively-small volume of blood removed from peripheral veins has been found sufficient for ultrafiltration for most CHF patients suffering from fluid overload.
Clinical trials of ultrafiltration in CHF patients have been performed using standard and novel devices for peripheral access to blood. Ultrafiltration using peripheral vein access with standard needles or catheters has recently successfully treated several CHF patients. However, standard peripheral vein access has not been successful for all CHF patients. The peripheral vein access had been performed using conventional short (3-4 cm long) catheters inserted into a peripheral vein in the arm of the patient. The peripheral veins in some CHF patients have such poor blood flow that the veins collapse around the area of the catheter tip when short peripheral catheters were used to continuously draw blood for ultrafiltration. For these patients, the blood in the peripheral veins available for withdrawal is not a sufficient for ultrafiltration. These CHF patients require some other blood withdrawal mechanism to remove fluids from their blood stream and provide relief from fluid overload. Accordingly, there is a need for ultrafiltration devices for patients having poor blood flow through their peripheral veins that is inexpensive, relatively easy to apply and does not require a hospital ICU.
There is a need for a simplified removal of excess fluid from fluid overloaded patients that have poor blood flow in their peripheral veins. For those patients having poor blood flow in peripheral veins, devices and methods have been developed and are disclosed here to remove excess fluids through extended length blood access catheters introduced via a peripheral vein, for example, in the patient""s arm. These devices and methods safely continuously withdraw blood from a peripheral vein at substantially higher flow rates than the peripheral vein would normally permit. The volume of blood withdrawn from the venous system of a patient through a catheter inserted into a peripheral vein is sufficient for ultrafiltration and fluid overload relief, even for those patients having poor blood flow in their peripheral veins. These devices and methods are safer and simpler than the traditional central vein access catheters.
In forty percent (40%) to eighty percent (80%) of relatively young and healthy people with good veins, continuous blood flow of 40 to 120 mL/min (milliliters per minute) can be established via standard short length (3-4 cm) peripheral vein access needles or catheters. Peripheral veins in the arm such as basilic, cephalic or antibrachial vein are often used to infuse medication or to draw blood from a patient. Patients are commonly asked to increase their blood supply to the arm by squeezing a rubber ball to improve the blood withdrawal. This method using short length catheters is commonly used in extracorporeal blood treatment procedures such as aphaeresis. When patients and blood donors do not have appropriately large veins, they are usually not accepted for treatment. Where the treatment is lifesaving, such as in chemotherapy for blood cancer, central line catheters are placed to allow access to blood.
Based on clinical studies, peripheral vein access using short length catheters has had limited success for blood withdrawal to perform fluid removal in chronically ill CHF patients. Many CHF patients have poor blood flow through their peripheral veins. Effective fluid removal treatment for CHF patients generally requires fluid removal rate of 250 to 1000 mL/Hour. It has been discovered that the 500 mL/Hour fluid removal rate is preferred by physicians in CHF patients.
It is not practical to extract more than 20% to 30% of volume of blood as ultrafiltrate. This implies that to remove 500 mL/Hour (8.3 mL/min) of fluid from the patient, continuous blood flow of at least 40 mL/min through the filter is desired. Attaining this rate in many CHF patients can be difficult. CHF patients are typically elderly. The surface veins in the arms of many CHF patients have been punctured many times during prior medical treatments, and the veins often have stenosis. Moreover, as a result of heart failure, these patients have reduced cardiac output (i.e., total amount of blood pumped by the heart). In response to their poor cardiac output, the circulatory system of these patients reduces the blood supply to peripheral organs (including the arms and the hands), in order to maintain an adequate blood supply to the brain, heart and other vital organs.
Applicants determined that the difficulties with withdrawing blood at rates of 40 to 60 mL/min were due primarily to two conditions:
(a) Intermittent collapse of the peripheral vein around the tip of the withdrawal catheter needle. The vein collapse appears to have been due (at least in part) to the small caliber of the surface peripheral veins used for withdrawal and low venous pressure in the vein. Suction of blood at the tip of the catheter generated a negative pressure zone in the blood and caused intermittent vein collapse. The collapse of the vein prevents withdrawal of blood until the vein returned to its original shape. This first condition could be compensated for in some CHF patients by straightening or relaxing the arm of the patient.
(b) Flow demand determined by the pump in the ultrafiltration device exceeded the blood supply available to the peripheral vein being used for withdrawal. Because the pump demanded a flow of blood more than was available in the peripheral vein, a negative pressure resulted that collapsed the vein. While the pump controller had automatic feedback that reduced the pump speed when the pressure in the withdrawal tube began to drop, the feedback controller could not adequately compensate for the inadequate blood flow through the peripheral vein in some CHF patients.
Based on experiments, it was concluded that a fundamental problem of blood withdrawal from a peripheral vein is the dependence on the drainage from the arm and the hand for blood supply. The available blood flow for withdrawal in a surface peripheral vein is limited to the blood draining from the capillary system. If the blood draining from the capillary system is not sufficient for ultrafiltration treatment, then using conventional local peripheral vein access to withdraw blood becomes unworkable. This problem of inadequate drainage of blood from the capillary system is greatly exacerbated in CHF patients where the arterial blood supply to the arm is reduced compared to healthy subjects.
A solution to inadequate blood flow for withdrawal from peripheral veins is to withdraw blood from other regions of the circulatory system that have a generous supply of blood flow. For example, central catheters draw blood from the large pool of venous blood in the right atrium or the adjacent vena cava. Venous blood collected in these xe2x80x9cgreat vesselsxe2x80x9d is the combined drainage from all body organs. Even in a CHF patient with reduced cardiac output it is never less than 3 to 4 L/min. The caliber of these central vessels is large compared to the size of the catheter and continuous withdrawal of as much as 200 to 400 mL/min is possible, even for CHF patients.
Central venous catheters have been used to perform Renal Replacement Therapy and fluid removal in CHF patients. However, central venous catheters are difficult to inserting into a patient, require surgery and fluoroscopy to be inserted and removed and generally are closely monitored while a patient is in an ICU during the entire ultrafiltration treatment. Moreover, the risk associated with the placement of central venous catheters limit their use to critically ill patients. Central venous catheters are generally inserted as a life saving measure to relieve critically dangerous fluid overload conditions in CHF patients in danger of imminent death.
The inventive devices and methods disclosed here provide a means for relieving fluid overload in CHF patients who cannot be successfully treated with the conventional peripheral vein blood withdrawal but in whom the placement of central catheters is not desired or justified. The devices and methods developed by applicants combine the access to a large pool of blood (an advantage of central catheters) with the ease and safety of the peripheral vein access. By combining the advantages of central catheter access and peripheral vein access, the present invention provides a technique for providing ultrafiltration (or other RRT treatment such as slow continuous hemofiltration at modest replacement rates) for those patients that have inadequate blood flow in their peripheral veins outside of the ICU environment.
Theoretically, all veins in the human body are connected. The network of veins in a human body include a trunk vessel (central venous cavity) connected to the right atrium of the heart. From the central venous cavity extends many branches of veins that each branch progressively to smaller and smaller veins until the veins become tiny capillaries that connect to the arterial circulatory system. In the venous system, blood drains from the capillaries and flows to the progressively larger veins until all veins drain into the large flow of the central venous cavity. Thus, the largest supply of blood in the venous system is downstream of the blood flow, which is ultimately the central venous cavity. In contrast, the largest supply of blood in the arterial system is upstream because blood flows from the central arteries and downstream towards the capillaries.
In the venous system, it would be useful to draw blood from the downstream sources of venous blood. However, to draw blood from downstream of the peripheral vein from the location near the insertion point of a catheter would require that blood flow backward from the central venous pool through the network of branching vessels into the catheter. Drawing venous blood from downstream in a vein is a technique known as retrograde (opposite to the natural direction) flow. In contrast to retrograde flow, antegrade flow is the withdrawal of blood in the same direction as the natural flow of blood.
Retrograde blood withdrawal from the peripheral vein in an arm (or other body extremity) where these veins come to the body surface and where the traditional catheters are inserted is almost impossible because the peripheral veins in arms and legs prevent retrograde flow and do not allow for blood to flow upstream to a catheter tip intake opening. Peripheral veins have a series of one-way valves (venous flapper valves) along their path. These one-way valves prevent retrograde flow, and prevent venous blood from the central venous cavity flowing upstream through the vein towards the catheter tip. The valves are spaced along the length of the peripheral vessels. The valves are constructed of flappers or leaves that can be bent easily in the downstream direction to permit the downstream flow of blood. The flappers shut closed if the flow of blood reverses and this closure prevents the upstream (retrograde) flow of blood through peripheral veins.
The natural purpose of venous flapper valves is to prevent retrograde blood flow when a person moves and thereby applies inertia and centrifugal forces to the blood in the veins. The valves also prevent pooling of blood at the lower extremities, e.g., hands and feet, due to the force of gravity. In patients that have defective xe2x80x9cincompetentxe2x80x9d venous valves, it is common to see bulging distended veins in the legs. These venous valves, which appear to work quite well in some CHF patients, prevent retrograde flow of blood to a short peripheral catheter inserted into the arm of a CHF patient. It is believed that the venous flappers are a principal reason why retrograde flow is prevented when a peripheral catheter applies a local negative pressure in a peripheral vein. Accordingly, there is a need to overcome or circumvent the natural venous flappers. By circumventing these flappers, a peripherally inserted catheter should be able to create a sufficient negative pressure to cause retrograde blood flow and, thus, increase the blood flow through a catheter for ultrafiltration treatment without collapsing the vein.